Document Detail


Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds.
MedLine Citation:
PMID:  18070820     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present work explores cell cultivation in macroporous alginate scaffolds as a means to reproduce hepatocyte terminal differentiation in vitro. Newborn rat liver cell isolates, consisting of proliferating hepatocytes and progenitors, were seeded at high cell density of 125 x 10(6)/cm(3) within the scaffold and then cultivated for 6 wk in chemically defined medium. Within 3 days, the alginate-seeded cells expressed genes for mature liver enzymes, such as tryptophan oxygenase, secreted a high level of albumin, and performed phase I drug metabolism. The cells formed compacted spheroids, establishing homotypic and heterotypic cell-to-cell interactions. By 6 wk, the spheroids developed into organoids, with an external mature hepatocyte layer covered by a laminin layer encasing inner vimentin-positive cells within a laminin-rich matrix also containing collagen. The hepatocytes presented a distinct apical surface between adjacent cells and a basolateral surface with microvilli facing extracellular matrix deposits. By contrast, viable adherent cells within collagen scaffolds presenting the identical porous structure did not express adult liver enzymes or secrete albumin after 6 wk. This study thus illustrates the benefits of cell cultivation in macroporous alginate scaffolds as an effective promoter for the maturation of newborn liver cells into functional hepatic tissue, capable of maintaining prolonged hepatocellular functions.
Authors:
Mona Dvir-Ginzberg; Tsiona Elkayam; Smadar Cohen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-10
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  22     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-05-28     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1440-9     Citation Subset:  IM    
Affiliation:
Ben-Gurion University of the Negev, Department of Biotechnology Engineering, P.O. 653, Beer-Sheva 84105, Israel.
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MeSH Terms
Descriptor/Qualifier:
Alginates*
Animals
Animals, Newborn
Cell Differentiation
Cytochrome P-450 Enzyme System / metabolism
Hepatocytes / cytology*
Liver / growth & development*
Microscopy, Electron, Transmission
Rats
Rats, Sprague-Dawley
Stem Cells / cytology
Tissue Engineering / methods*
Chemical
Reg. No./Substance:
0/Alginates; 9035-51-2/Cytochrome P-450 Enzyme System

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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